Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effectiveness of conventional neuroleptics in schizophrenia is often limited by extrapyramidal side effects (EPS), which are known to contribute to poor compliance and relapse. However, there is now evidence that drugs that block 5-HT2 receptors as well as D2 receptors have better EPS profiles. Risperidone has these pharmacologic properties. In two large clinical trials, risperidone (2, 6, 10, 16 mg/day or 4, 8, 12, 16 mg/day) was compared with either placebo and haloperidol (20 mg/day) or risperidone (1 mg/day) and haloperidol (10 mg/day). Extrapyramidal side effects were assessed using the Extrapyramidal Symptom Rating Scale and by recording the use of anticholinergic medication. Other adverse effects were assessed using the UKU Side Effects Scale. In both studies, the severity of EPS in the risperidone groups was significantly less than in the haloperidol group. In the placebo-controlled study, doses of 2 and 6 mg/day of risperidone produced no worse EPS than placebo. Other side effects were minor, and included brief hypotension (mediated via alpha-blockade) and weight gain. Overall, risperidone at antipsychotic doses was better tolerated than haloperidol.
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PMID:Extrapyramidal side effects and tolerability of risperidone: a review. 752 Sep 6

Risperidone, a benzisoxazole derivative, is a novel antipsychotic agent that has an extremely strong binding affinity for serotonin 5-HT2 receptors, a strong binding affinity for dopamine D2 receptors, and a high affinity for alpha 1- and alpha 2-adrenergic receptors and histamine H1 receptors. Its affinity for serotonin receptors is approximately 200 times greater than that of haloperidol, and its dopamine antagonistic potency is comparable to that of haloperidol. Its major metabolite, 9-hydroxyrisperidone, has similar pharmacologic activity, and thus the parent compound and metabolite form the active antipsychotic moiety. Clinical trials demonstrate that risperidone is an effective antipsychotic agent that improves negative as well as positive symptoms of schizophrenia. At recommended dosages, the frequency of extrapyramidal side effects is no greater than that seen with placebo. The drug appears to be an advance in the treatment of psychoses.
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PMID:Risperidone. 752 43

Risperidone, a benzisoxazol derivative, is a novel antipsychotic agent which combines potent serotonin (5-hydroxytryptamine) 5-HT2 and dopamine D2 receptor antagonism. Development of the drug was stimulated by reports that the selective serotonin 5-HT2 antagonist ritanserin improved the negative symptoms of schizophrenia and decreased extrapyramidal symptoms when combined with haloperidol. The relatively low incidence of extrapyramidal symptoms with risperidone may reflect a preferential action on mesolimbic rather than nigrostriatal dopaminergic pathways. Recent clinical investigation suggests that risperidone is of at least comparable efficacy to haloperidol and perphenazine in improving the symptoms of acute and chronic schizophrenia on short term administration. Advantages offered by risperidone over haloperidol include a faster onset of antipsychotic action, a lower incidence of extrapyramidal effects and possibly greater efficacy against the negative symptoms of schizophrenia. If these benefits prove to be maintained during long term therapy, risperidone is likely to make a significant contribution to the treatment of schizophrenia.
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PMID:Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. 752 27

It has been suggested that a combined blockade of 5-HT2 and D2 dopamine receptors may be superior to D2 dopamine antagonists alone in the treatment of schizophrenia. Risperidone, which has a high affinity for 5-HT2 and D2 dopamine receptors in vitro, is a new antipsychotic drug that has been developed according to this hypothesis. The aim of this study was to examine if risperidone indeed induces 5-HT2 and D2 dopamine receptor occupancy in vivo in humans. Central receptor occupancy was examined by positron emission tomography (PET) in three healthy men after oral administration of 1 mg risperidone. [11C]N-methylspiperone ([11C]NMSP) was used as a radioligand for determination of 5-HT2 receptor occupancy in the neocortex. Both an equilibrium ratio analysis and a kinetic three-compartmental analysis indicated a 5-HT2 receptor occupancy about 60%. [11C]raclopride was used as a radioligand for determination of D2 dopamine receptor occupancy in the striatum and the calculated occupancy was about 50%. This is the first quantitative determination of 5-HT2 receptor occupancy induced by an antipsychotic drug in the living human brain. The results indicate that 5-HT2 receptor occupancy should be very high at the dose level of 4-10 mg risperidone daily, as suggested for clinical use. Risperidone is thus an appropriate compound for clinical evaluation of the benefit of combined 5-HT2 and D2 dopamine receptor blockade in the treatment of schizophrenia.
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PMID:5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone. 753 Mar 76

In this study, we investigated whether risperidone, a serotonin-S2A (5-HT2A)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both resperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) produced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3-10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.
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PMID:Effects of risperidone on phencyclidine-induced behaviors: comparison with haloperidol and ritanserin. 753 32

Risperidone, a novel antipsychotic with high binding affinity for serotonin 5-HT2 and a lesser affinity for dopamine D2 receptors, is described and clinical studies are reviewed. In two large-scale trials in North America and Europe, risperidone 6 mg and 4 mg to 8 mg/day compared favourably with haloperidol 20 mg or 10 mg/day in controlling the positive symptoms of schizophrenia. In the North American trial, risperidone produced a significant improvement in negative symptoms; no comparable improvement was reported among haloperidol-treated patients. Risperidone would, thus, appear to offer a potential advantage over other neuroleptics, although the place of this new compound in the pharmacological armamentarium of schizophrenia must be clarified in clinical practice.
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PMID:Risperidone: neurochemical, pharmacologic and clinical properties of a new antipsychotic drug. 753 51

By the use of positron emission tomography (PET), high central dopamine D2 receptor occupancy (70 to 90%) has been demonstrated in patients treated with conventional neuroleptics. In patients treated with the atypical antipsychotic clozapine, the D2 occupancy was low (20 to 67%). The effects of clozapine may thus be mediated by a mechanism distinct from D2 occupancy. The observation that low doses of clozapine (125 to 175 mg daily) induced more than 80% (5-hydroxytryptamine) 5-HT2 occupancy supports the view that 5-HT2 antagonism may be related to the atypical effects of clozapine. Risperidone is a new antipsychotic drug with high affinity in vitro for both central 5-HT2 and D2 receptors. In this study, we determined the D2 and 5-HT2 occupancy induced by clinical treatment with risperidone. Four patients with acute exacerbation of schizophrenia were examined by PET after 4 weeks of treatment with risperidone, 6 mg daily. The D2 occupancy in the striatum was 75 to 80%. The 5-HT2 occupancy in the neocortex was 78 to 88%. This study confirms that, in patients with schizophrenia, treatment with risperidone induces a high D2 and 5-HT2 occupancy. Risperidone is, accordingly, a suitable drug for the examination of the clinical benefit of combined serotonin and dopamine antagonism.
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PMID:Positron emission tomography studies on D2 and 5-HT2 receptor binding in risperidone-treated schizophrenic patients. 753 84

Serotonin-dopamine antagonists (SDAs) offer the possibility of improved treatment of schizophrenia compared with conventional neuroleptics and have superior safety profiles. Clinical trial data have so far been published for only three SDAs to date, namely, risperidone, sertindole, and olanzapine. Of these, extensive data are available only for risperidone, showing that at doses of 4 to 16 mg/day, it is superior to haloperidol at 10 to 20 mg/day. Furthermore, risperidone, 6 and 16 mg/day, significantly improved negative/symptoms, whereas 20 mg/day of haloperidol was ineffective. Risperidone also appears to cause fewer extrapyrimidal symptoms (EPS) than haloperidol, 10 or 20 mg/day. Similar advantages of risperidone over perphenazine have also been found. A clinical trial of sertindole showed that, at 20 mg/day, it was equivalent to haloperidol, 16 mg/day, and caused fewer EPS. Olanzapine, a chemical derivative of clozapine, has also been shown to be superior to haloperidol (10 to 20 mg/day) at doses of 7.5 to 17.5 mg/day. In addition, at doses of 12.5 to 17.5 mg/day, olanzapine was found to have a significantly superior effect on negative symptoms over haloperidol, 10 to 20 mg/day. Doses of up to 17.5 mg/day of olanzapine also caused fewer EPS than haloperidol, 10 to 20 mg/day. There was no evidence of any leukopenia in patients treated with olanzapine in this small study (N = 335). The low EPS liability of these SDAs, combined with their efficacy, suggests that SDAs should become the mainstay of treatment for schizophrenia.
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PMID:Clinical efficacy of serotonin-dopamine antagonists relative to classic neuroleptics. 753 85

This study compares the antipsychotic efficacy and the tolerability of risperidone and clozapine in patients with schizophrenia. Patients were randomized to double-blind treatment with risperidone, 4 mg (N = 20), risperidone, 8 mg (N = 19), or clozapine, 400 mg (N = 20), daily for 28 days. Efficacy was assessed by improvement of psychotic symptoms, measured on the Brief Psychiatric Rating Scale, and Clinical Global Impression. The tolerability was assessed by the Simpson and Angus scale for extrapyramidal side effects (EPS), the Association for Methodology and Documentation in Psychiatry (AMDP) scale for somatic side effects, spontaneous reports of adverse events, clinical laboratory assessments, and vital signs. All treatments reduced psychotic symptoms. The global tolerability was significantly better in the risperidone than in the clozapine-treated patients (p < 0.01). There were no differences between treatments on the AMDP scale. The most frequent spontaneously reported adverse effects were dizziness, fatigue, accommodation disturbance, and EPS in all treatment groups and increased salivation, mainly in the clozapine-treated patients. Although there were no changes in vital signs during risperidone treatment, clozapine was associated with a mean reduction in heart rate of 10 beats/minute. Risperidone tolerability at endpoint was classified as "very good" by 60 and 47% of patients treated with risperidone, 4 and 8 mg daily, respectively; the corresponding figure in clozapine-treated patients was 30%. The results suggest that risperidone is at least as effective as an antipsychotic as clozapine, providing a valuable new approach for the treatment of schizophrenia.
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PMID:Randomized, double-blind, controlled trial of risperidone versus clozapine in patients with chronic schizophrenia. 753 87

Risperidone, the latest agent in the continuing search for a better antipsychotic drug, seems to be an important addition to our treatment armamentarium for several reasons. First, risperidone is as effective as traditional antipsychotics for treating schizophrenia and perhaps more effective for treating refractory schizophrenia. Second, and related to the first point, risperidone is effective in the treatment of the negative symptoms of schizophrenia. Third, risperidone has a superior side-effect profile causing relatively few, if any, EPSEs. Fourth, risperidone may have an antidyskinetic property that, rather than simply not causing tardive dyskinesia, may actually improve those symptoms.
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PMID:Risperidone: the search for a better antipsychotic. 753 23


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